The goal of the proposed research is to isolate and characterize the macromolecular composition of those specific types of synapses which contain Protein I, a recently isolated "synapse-specific" protein, whose phosphorylation is regulated by cyclic AMP-dependent protein kinase. To isolate such specific types of synapses, a highly purified preparation of the synaptic junctional complex and synaptic vesicles, derived from various types of synapses in the central nervous system, will be applied to an antiProtein I antibody-coupled immunoadsorbent column; Protein I-containing junctional complex and synaptic vesicles bound to the column will then be eluted appropriately. The specific types of synaptic junctional complex and synaptic vesicles thus isolated will be characterized with respect to (a) various enzymes including neurotransmitter-sensitive adenylate cyclases, cyclic AMP-dependent Protein I kinase, Protein I phosphatase, and glycosyltransferase; (b) various proteins including Protein I and other phosphoproteins, a specific protein coupled to Protein I, neurotransmitter receptors and glycoproteins. It is hoped that these studies will contribute to an understanding at the molecular level of those synapses whose activity is modulated by cyclic AMP and its related enzymes and proteins. It is also hoped that the detailed analyses of the macromolecular constituents associated with such synapses will be of value in exploring further clarification of the molecular mechanisms of certain neurological and psychiatric disorders that involve the malfunction of catecholaminergic and other neurotransmitter systems.